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Transplantation of Cultured Stem Cell as an Optimal Treatment for Limbal Stem Cell Deficiency

Review of “Long‐Term Results of Cultured Limbal Stem Cell Versus Limbal Tissue Transplantation in Stage III Limbal Deficiency” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Researchers led by Vincent M. Borderie (Sorbonne Université, Paris, France) recently developed the transplantation of limbal stem cells (LSCs) cultured on human amniotic membrane with no feeders [1, 2] as a treatment for the impaired homeostasis of the corneal epithelium caused by a loss of proper function of corneal epithelial stem cells, otherwise known as limbal stem cell deficiency (LSCD) [3]. A subsequent clinical trial aimed to evaluate the clinical outcomes of employing this technique in terms of improvements to visual function, ocular surface condition, handicap status, and limbal epithelial function, while also monitoring possible side effects in patients with stage III LSCD, defined as unilateral or bilateral total limbal deficiency [4].

Now the authors report the data from this clinical trial alongside a comparison to a retrospective group of patients who underwent autologous or allogeneic limbal tissue transplantation at the same institution in a new STEM CELLS Translational Medicine article [5].

The details of the trial outcomes and comparative data include the following data:

  • The authors assessed thirty eyes with stage III LSCD treated by:
    • Autologous (autoLSC) or allogeneic (alloLSC) cultured LSC transplantation (prospective phase II clinical trial; average follow‐up time, 72 months)
    • Autologous (autoLT) or allogeneic (alloLT) limbal tissue transplantation (retrospective control group; average follow‐up time, 132 months)
  • The trial found a five-year graft survival, defined by the absence of recurrence of the clinical signs of LSCD, of 71% for autoLSC, 0% for alloLSC, 75% for autoLT, and 33% for alloLT transplantation
  • Visual acuity significantly improved for autoLSC and autoLT but decreased for alloLSC and alloLT transplantation
  • While corneal epithelial defect represented the only adverse event recorded after autoLSC transplantation, patients from the remaining three groups suffered from severe sight‐threatening adverse events
    • Successful grafts featured a greater in the levels of chronic epithelial defects, greater superficial vascularization‐free corneal area, lower variability of the corneal epithelial thickness, and higher corneal epithelial basal cell density

Overall, the authors established that while autologous cultured LSC transplantation associated with overall safety and high long‐term survival and dramatic improvement in vision, autologous limbal tissue transplantation provided similar benefits with lower safety, and cadaveric allogeneic grafts resulted in low long‐term success rate and a high prevalence of serious adverse events. 

However, the authors do note some limitation to their study, which include the study population size, the use of a retrospective control group, and the absence of both a simple limbal epithelial transplantation group, a challenging technique for cell therapy technologies [6], and a cultivated autologous oral mucosal epithelial cell transplantation group, which may represent an exciting alternative to allogeneic cultured LSC transplantation if long‐term follow‐up of patients match the encouraging short‐term results.

For more on the power of stem cell transplantation as a treatment for vision loss, stay tuned to the Stem Cells Portal!

References

  1. Ghoubay-Benallaoua D, Basli E, Goldschmidt P, et al., Human epithelial cell cultures from superficial limbal explants. Molecular Vision 2011;17:341-54.
  2. Ghoubay-Benallaoua D, Sandali O, Goldschmidt P, et al., Kinetics of Expansion of Human Limbal Epithelial Progenitor Cells in Primary Culture of Explants Without Feeders. PLoS ONE 2013;8:e81965.
  3. Le Q, Xu J, and Deng SX, The diagnosis of limbal stem cell deficiency. The Ocular Surface 2018;16:58-69.
  4. Deng SX, Borderie V, Chan CC, et al., Global Consensus on Definition, Classification, Diagnosis, and Staging of Limbal Stem Cell Deficiency. Cornea 2019;38:364-375.
  5. Borderie VM, Ghoubay D, Georgeon C, et al., Long-Term Results of Cultured Limbal Stem Cell Versus Limbal Tissue Transplantation in Stage III Limbal Deficiency. STEM CELLS Translational Medicine 2019;8:1230-1241.
  6. Sangwan VS, Basu S, MacNeil S, et al., Simple limbal epithelial transplantation (SLET): a novel surgical technique for the treatment of unilateral limbal stem cell deficiency. British Journal of Ophthalmology 2012;96:931.